Multimeric Nanocarrier Peptide Delivery

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Solution Overview

Problem

Current drug delivery systems face challenges in achieving efficient and targeted oral delivery of proteins and peptides due to poor pharmacokinetic properties, low permeability, and proteolytic instability, limiting their bioavailability and requiring invasive methods for administration.

Innovation Solution

A biodegradable multimeric nanocarrier system comprising covalently linked peptide monomers with functional groups and PEG linkers, designed for reversible or irreversible binding with bioactive agents, enhancing stability and permeability across intestinal and blood-brain barriers.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If proteins are administered orally, then the natural digestive process would spread absorption over hours, but proteins are digested in the gastrointestinal tract and cannot transit across the epithelial cell barrier

Engineering Contradiction:

Improveoral administration convenienceVSAvoidprotein stability and permeability

Core Design Contradiction:

Ease of operationVSReliability

Solution Approach 1:

The patent employs nanocarrier systems as intermediary vehicles to protect proteins from digestive degradation and facilitate their transport across the intestinal epithelial barrier. These nanocarriers serve as mediators that shield the protein payload from harsh gastrointestinal conditions while enabling controlled release and absorption.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention modifies the physical and chemical parameters of protein delivery by formulating proteins into nanocarrier systems with specific size ranges (10-200 nm), surface charges, and compositional characteristics. These parameter changes enable the proteins to withstand digestive conditions and enhance their permeability across biological barriers.

Inventive Principle:

Principle #35Parameter changes

2Reliability

If proteins are administered via injection, then they can be delivered directly into the bloodstream, but most proteins have a very short half-life measured in minutes

Engineering Contradiction:

Improvedirect delivery efficiencyVSAvoidprotein half-life

Core Design Contradiction:

ReliabilityVSDuration of action of moving object

Solution Approach 1:

The nanocarrier systems provide continuous protection and sustained release of proteins, extending their circulation time and biological half-life. The controlled release mechanism ensures continuous therapeutic action rather than rapid clearance, maintaining effective drug levels for extended periods.

Inventive Principle:

Principle #20Continuity of useful action

Solution Approach 2:

The patent utilizes nanocarrier shells with flexible compositions (including lipid-based, polymeric, and hybrid structures) that protect the protein payload from rapid degradation and clearance. These flexible shell structures can be engineered to control release kinetics and extend circulation half-life.

Inventive Principle:

Principle #30Flexible shells and thin films

3Reliability

If permeation enhancers are used to improve intestinal permeability, then absorption of poorly absorbed compounds is enhanced, but the invasive nature and associated side-effects severely hamper their use

Engineering Contradiction:

Improveintestinal permeabilityVSAvoidside-effects and invasiveness

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent converts the naturally protective but barrier-forming tight junctions of the intestinal epithelium from obstacles into beneficial structures by using nanocarriers that can navigate through or alongside these junctions without causing damage. The system exploits natural transport mechanisms rather than forcibly disrupting barriers.

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

Solution Approach 2:

Nanocarriers serve as non-invasive intermediary systems that facilitate protein transport across the intestinal barrier without requiring harmful permeation enhancers. These mediators interact with natural transport pathways and cellular mechanisms to achieve permeability enhancement without side effects.

Inventive Principle:

Principle #24Intermediary (Mediator)

4Adaptability or versatility

If larger peptides are designed to overcome PepT1 transport limitations, then substrate specificity is avoided, but PepT1 can only transport smaller peptides less than 4 amino acid residues

Engineering Contradiction:

Improvepeptide size flexibilityVSAvoidtransporter compatibility

Core Design Contradiction:

Adaptability or versatilityVSReliability

Solution Approach 1:

The patent segments large peptide therapeutics into smaller peptide or peptidomimetic units that can be transported by PepT1, while maintaining the overall therapeutic function. These segmented units are then reassembled or released at the target site, overcoming the size limitation of PepT1 transporters.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The invention modifies the molecular parameters of peptide drugs by designing peptidomimetics with optimized size, charge, and structural characteristics that match PepT1 substrate requirements. These parameter changes enable transport through PepT1 while preserving therapeutic activity.

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentUS9421272B2Nanocarrier compositions and methods

Publication Date: 2016.08.23 RUTGERS THE STATE UNIV

AI summary

This invention provides multimeric nanocarrier for in vivo delivery of a bioactive agent, comprising at least two peptide monomers reversibly or irreversibly linked with one or more of said bioactive agents, wherein said two or more of said peptide monomers are covalently linked by a biodegradable difunctional moiety, as well as methods of using this nanocarrier.